The primary motor cortex electrical and chemical stimulation attenuates the chronic neuropathic pain by activation of the periaqueductal grey matter: The role of NMDA receptors

Author(s)

Negrini-Ferrari, Sylmara Esther ^{[1, 2, 3]} ; Medeiros, Priscila ^{[1, 2, 3]} ; Malvestio, Rafael Braghetto ^{[1, 2, 3]} ; Silva, Mariana de Oliveira ^{[1, 2, 3]} ; Medeiros, Ana Carolina ^{[1, 2, 3]} ; Coimbra, Norberto Cysne ^{[4, 1, 2, 3]} ; Machado, Helio Rubens ^{[2, 3, 5]} ; de Freitas, Renato Leonardo ^{[4, 1, 2, 3, 6]}

Affiliation

^[1] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Lab Neurosci Pain & Emot, Av Bandeirantes 3900, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Multiuser Ctr Neuroelectrophysiol, Dept Surg & Anat, Av Bandeirantes 3900, Ribeirao Preto, SP - Brazil

^[4] Behav Neurosci Inst INeC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Brain Protect Lab Childhood, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Fed Univ Alfenas UNIFAL MG, Biomed Sci Inst, Str Gabriel Monteiro da Silva 700, BR-37130000 Alfenas, MG - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 415, OCT 11 2021.
• Web of Science Citations: 0

Abstract

Background: Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP). Aims: This work aims to investigate if the MCS in the primary motor cortex (M-1) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, to elucidate if the persistent activation of N-methyl-D-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitisation of the NP. Methods: Male Wistar rats were submitted to the von Frey test to evaluate the mechanical allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve. The MCS was performed with low-frequency (20 mu A, 100 Hz) currents during 15 s by a deep brain stimulation (DBS) device. Moreover, the effect of M-1-treatment with an NMDAr agonist (at 2, 4, and 8 nmol) was investigated in CCI rats. The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS. Results: The MCS decreased the mechanical allodynia in rats with chronic NP. The M-1-treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. In addition, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS. Conclusion: The M-1 cortex glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling recruitting NMDAr located on PAG neurons in rodents with chronic NP. (AU)

• FAPESP's process: 14/07902-2 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany)
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 12/25167-2 - Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/13560-5 - Effect of deep brain stimulation and cannabidiol treatment in the subthalamic nucleus on the motors and non-Motors symptoms in the experimental model of Parkinson Disease
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral